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      GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

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          Abstract

          Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course.

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          Interneurons of the neocortical inhibitory system.

          Henry Markram, Maria Toledo-Rodriguez, Yun Wang … (2004)
          Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.
          Article 0 comments Cited 816 times – based on 0 reviews     Review now
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            Cortical inhibitory neurons and schizophrenia.

            David A. Lewis, Takanori Hashimoto, David W Volk (2005)
            Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
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              Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition.

              F Pouille, M Scanziani (2001)
              The temporal resolution of neuronal integration depends on the time window within which excitatory inputs summate to reach the threshold for spike generation. Here, we show that in rat hippocampal pyramidal cells this window is very narrow (less than 2 milliseconds). This narrowness results from the short delay with which disynaptic feed-forward inhibition follows monosynaptic excitation. Simultaneous somatic and dendritic recordings indicate that feed-forward inhibition is much stronger in the soma than in the dendrites, resulting in a broader integration window in the latter compartment. Thus, the subcellular partitioning of feed-forward inhibition enforces precise coincidence detection in the soma, while allowing dendrites to sum incoming activity over broader time windows.
              Article 0 comments Cited 295 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Christiaan H. Vinkers: URI : http://frontiersin.org/people/u/46091
                Hilleke E. Hulshoff Pol: URI : http://frontiersin.org/people/u/44734
                Anouk Marsman: URI : http://frontiersin.org/people/u/110880
                Journal
                Journal ID (nlm-ta): Front Psychiatry
                Journal ID (iso-abbrev): Front Psychiatry
                Journal ID (publisher-id): Front. Psychiatry
                Title: Frontiers in Psychiatry
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-0640
                Publication date (Electronic): 11 August 2017
                Publication date Collection: 2017
                Volume: 8
                Electronic Location Identifier: 118
                Affiliations
                [1] 1Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht , Utrecht, Netherlands
                [2] 2Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre , Hvidovre, Denmark
                Author notes

                Edited by: André Schmidt, King’s College London, United Kingdom

                Reviewed by: Fiorenzo Conti, Università Politecnica delle Marche, Italy; Fei Du, Harvard Medical School, United States

                *Correspondence: Anouk Marsman, anoukm@ 123456drcmr.dk

                Specialty section: This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                Article
                DOI: 10.3389/fpsyt.2017.00118
                PMC ID: 5554536
                PubMed ID: 28848455
                SO-VID: 457aae82-d290-43a2-90b7-02e8671fc48a
                Copyright © Copyright © 2017 De Jonge, Vinkers, Hulshoff Pol and Marsman.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 31 March 2017
                Date accepted : 22 June 2017
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 103, Pages: 12, Words: 9977
                Categories
                Subject: Psychiatry
                Subject: Review

                ScienceOpen disciplines: Clinical Psychology & Psychiatry
                Keywords: gaba,schizophrenia,magnetic resonance spectroscopy,postmortem studies,in vivo studies
                Data availability:
                ScienceOpen disciplines: Clinical Psychology & Psychiatry
                Keywords: gaba, schizophrenia, magnetic resonance spectroscopy, postmortem studies, in vivo studies

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